Athymic nude mice which cannot reject grafts of tumors including xenografts do not have a high incidence of spontaneous neoplasms. But, when nudes are grafted with a normal thymus, tumors, particularly lymphomas, are often seen. Congenic CBA and CBA-nude (inbred strains that are genetically virtually identical except that one carries the nude mutation) will be maintained in a specific pathogen free environment to insure longevity for the nude mice. Neonatal nudes will be given thymus grafts. The incidence of tumors in these mice will be compared to littermate nudes and normals, both grafted and intact. Both histocompatible and incompatible thymus will be grafted to determine if alloantigenic stimulation is important. Apparent lymphomas and leukemias will be tested for T cell and B cell antigenic markers. The presence of oncogenic virus in the tumors will be looked for by (a) attempts to passage the tumor to mice using cell free tumor extracts; (b) electron microscopic search of the tumor for C type virus; (c) the X-C cell cytopathogenicity assay; (d) a search for the virus associated cell surface antigen (GCSA) using a cytotoxic assay; (e) a search for a virus protein (gs) using a radioimmunoassay. A search for C type RNA virus in tumor free nude mice, both intact and grafted will be made using these techniques. In addition, some mice will be deliberately infected with Gross leukemia virus in order to induce tumor formation. The response to the DNA oncogenic virus SV40 by nude mice and nude cells growing in culture will be studied. Fibroblast cultures will be infected with SV40 and foci of transformation will be looked for. The ability of these cells to be infected by this virus will be determined by the presence of the nuclear (T) antigen. If cells are transformed in vitro, they will be injected into nudes to see if tumors can be established. Neonatal nude mice will be injected with SV40 virus in a direct attempt to induce tumors in vivo. If these mice fail to develop neoplasma, evidence for cell mediated immunity, an antibody to both transformed cells and virus will be sought. BIBLIOGRAPHIC REFERENCES: Lukic, M.L., Wortis, H.H., and Leskowitz, S. A gene locus affecting tolerance to BGG in mice. Cellular Immunology 15: 457, 1975.